Follicle-stimulating hormone insensitivity

Overview

Follicle-Stimulating Hormone (FSH) Insensitivity, also known as FSH receptor insensitivity or FSH resistance, is a rare endocrine disorder in which the body's reproductive tissues fail to respond appropriately to follicle-stimulating hormone. FSH is essential for normal sexual development and reproductive function in both males and females. In FSH insensitivity, mutations in the FSH receptor gene result in partial or complete inability of the ovaries or testes to respond to circulating FSH, leading to infertility and abnormal development of reproductive organs.

Causes

The primary cause of FSH insensitivity is mutations in the FSHR gene, which encodes the follicle-stimulating hormone receptor. These mutations impair receptor function, disrupting the hormonal signaling required for follicular development in females and spermatogenesis in males. The condition is typically inherited in an autosomal recessive manner, meaning both copies of the gene must be altered for the syndrome to manifest.

Symptoms

The symptoms of FSH insensitivity vary between males and females and depend on the degree of receptor dysfunction:

In Females

• Primary amenorrhea (absence of menstruation)

• Delayed or absent puberty

• Infertility

• Small or underdeveloped ovaries

• Low estrogen levels despite elevated FSH

• Normal external genitalia

In Males

• Variable spermatogenic failure

• Infertility or subfertility

• Normal testosterone levels and secondary sexual characteristics

• Small testicular size in some cases

Diagnosis

Diagnosis of FSH insensitivity involves hormonal testing, imaging studies, and genetic analysis. Key diagnostic steps include:

• Hormonal profile: Elevated serum FSH levels with low estradiol (in females) or impaired spermatogenesis (in males) suggest resistance.

• Pelvic ultrasound: May show small or underdeveloped ovaries with no follicular development in females.

• Semen analysis: In males, may show azoospermia (no sperm) or oligospermia (low sperm count).

• Genetic testing: Confirmation by identifying pathogenic mutations in the FSHR gene.

• Physical examination: Evaluation of pubertal development and reproductive anatomy.

Treatment

Treatment options for FSH insensitivity are limited and depend on the severity of the receptor dysfunction and the patient’s reproductive goals. Management strategies include:

• Hormone replacement therapy (HRT): Estrogen replacement in females to induce and maintain secondary sexual characteristics and bone health.

• Assisted reproductive technologies (ART): In some cases, in vitro fertilization (IVF) using donor oocytes may be an option for women.

• Gonadotropin therapy: Limited effectiveness in individuals with complete receptor insensitivity.

• Counseling and support: For emotional and psychological aspects related to infertility or delayed puberty.

• Monitoring: Regular evaluation of bone density, cardiovascular health, and hormone levels.

Prognosis

The prognosis for individuals with FSH insensitivity depends on the severity of receptor dysfunction. While fertility is usually significantly impaired, especially in females, hormone replacement can help manage symptoms and support normal physical development. Males with partial receptor function may retain some fertility. Early diagnosis and personalized treatment can improve quality of life and prevent complications related to hormone deficiencies.